REGULAR ARTICLE Automation of AMOEBA polarizable force field parameterization for

Abstract A protocol to generate parameters for the AMOEBA polarizable force field for small organic mole-cules has been established, and polarizable atomic typing utility, Poltype, which fully automates this process, has been implemented. For validation, we have compared with quantum mechanical calculations of molecular dipole moments, optimized geometry, electrostatic potential, and conformational energy for a variety of neutral and charged organic molecules, as well as dimer interaction energies of a set of amino acid side chain model compounds. Fur-thermore, parameters obtained in gas phase are substanti-ated in liquid-phase simulations. The hydration free energy (HFE) of neutral and charged molecules have been calcu-lated and compared with experimental values. The RMS error for the HFE of neutral molecules is less than 1 kcal/ mol. Meanwhile, the relative error in the predicted HFE of salts (cations and anions) is less than 3 % with a correlation coefficient of 0.95. Overall, the performance of Poltype is satisfactory and provides a convenient utility for applica-tions such as drug discovery. Further improvement can be achieved by the systematic study of various organic com-pounds, particularly ionic molecules, and refinement and expansion of the parameter database